نوع مقاله : مقاله پژوهشی

نویسندگان

مرکز تحقیقات کشاورزی و پزشکی هسته‌ای، سازمان انرژی اتمی ایران، صندوق پستی: 498- 31485، کرج- ایران

چکیده

یکی از مهمترین رادیوداروهای حاوی رادیوایزوتوپهای مس که در حال حاضر به صورت آزمایشی به مصارف بالینی می‌رسد، رادیوداروی «پیروآلدئید بیس ـ(4Nـ متیل تیوسمی کاربازون)»(Cu-PTSM) است. در این کار پژوهشی مراحل تولید رادیوایزوتوپ مس-61 به صورت محصول بمباران روی طبیعی در اثر واکنش هسته‌ای Cu61natZn(p,xn) به وسیلة پروتونهای شتاب گرفته در سیکلوترون با انرژی 22 مگا الکترون ولت و شدت جریان 150 میکرو آمپر، که منجر به تولید مس-61 با آکتیویته 6.33  کوری و بهره تولید حدود 33.3  میلی کوری بر میکروآمپر- ساعت گردید توصیف شده، سپس سنتز و تأیید کامل ساختار مولکولی مادّه چنگکی پیروآلدئید بیس ـ(4ـ Nـ متیل تیوسمی کاربازون) به روشهای طیف سنجی، و در نهایت نشاندارسازی آن با مس-61 به صورت کلرید گزارش شده است. در این بررسی، کنترل کیفی کامل رادیودارو به منظور اطمینان از قابلیت تزریق آن به موجود زنده نیز انجام شد.

کلیدواژه‌ها

عنوان مقاله [English]

Preparation and Quality Control of [61Cu]Pyruvaldehyde-Bis (N4-Methylthiosemicarbazone) Complex for PET Diagnosis

نویسندگان [English]

  • A.R Jalilian
  • P Rowshanfarzad
  • M Sabet
  • M Kamalidehghan
  • M Mirzaii
  • A.A Rajamand

چکیده [English]

Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM)‍ is the most important copper radiopharmaceutical used in clinical experiments. In this work, Copper-61 (T1/2=3.33 h) production process was accomplished via the nat.Zn(p,xn)61Cu, using 22MeV protons, and the current of 150 μA, resulted in 6.33 Ci of copper-61 with the production yield of 33.3 mCi/μAh. The complexing agent, PTSM, was synthesized and its structure was confirmed by the common spectroscopic methods, followed by radiolabeling with 61Cu-CuCl2. The final radiopharmaceutical solution underwent common quality control tests for animal injection. 

کلیدواژه‌ها [English]

  • copper-61
  • radiopharmaceuticals
  • nuclear reactions
  • copper compounds
  • quality control
  • 61Cu-PTSM
  • PET
  1. 1.       S. Mirzadeh, L.F. Mausner, S.C. Srivastava, “Production of No-Carrier Added 67Cu,” Int. J. Appl. Radiat Isot . 37(1), 29-36 (1986).

 

  1. 2.       D.W. McCarthy, L.A. Bass, P.D. Cutler, R.E. Shefer, R.E. klinkowstein, P. Herrero, J. S. Cutler, C.J. Anderson, M. J. Welch, “High purity production and potential applications of copper-60 and copper-61,” Nucl. Med. Biol. 26, 351-358 (1999).

 

  1. 3.       C.S. Cutler, J.S. Lewis, C.J. Anderson, “Utilization of metabolic, transport and receptor-mediated processes to deliver agents for cancer diagnosis,” Advanced Drug Delivery Reviws. 37, 189-211 (1999).

 

  1. 4.       F. Szelecsényi, K. Suzuki, Z. Kovács, M. Takei, K. Okada, “Production possibility of 60,61,62Cu radioisotopes by alpha induced reactions on cobalt for PET studies,” Nucl. Inst. Meth. [b]., 187, 153-163 (2002).

 

  1. 5.       H. Muramatsu , E. Shirai , H. Nakahara, Y.Murakami, “Alpha particle bombardment of natural nickel target for the production of 61Cu,” Int. J. Appl. Radi. Isot. 29, 611-614 (1978).

 

  1. 6.       F. Szelecsényi, G. Blessing, M. Qaim, “Excitation functions of proton induced nuclear reactions on enriched 61Ni and 64Ni: possibility of production of no-carrier-added 61Cu and 64Cu at a small cyclotron,” Int. J. Appl. Radi. Isot. 44(3), 575-580 (1993).

 

  1. 7.       R.B. Firestone, V.S. Shirley, C.M. Baglin, J. Zipkin, “Table of isotopes,” 8th edition, John Wiley and Sons, New York, 1447 (1996).

 

  1. 8.      A.B. Packard, “Synthesis and biodistribution of monocationic diiminedioxime copper complexes,” Nucl. Med. Biol. 25, 531-537 (1998).

 

  1. 9.      A.B. Packard, “Lipophilic cationic copper complexes as PET radiopharmaceuticals,” Int. J. Labeled. Compd & radiopharm. 40, 484-486 (1997).
  2. 10.   M.E. Shelton, M.A. Green, C.J. Mathias, M.J. Welch, “Kinetics of copper-PTSM in isolated hearts: A novel tracer for measuring blood flow with positron emission tomography,” J. Nucl. Med. 30(11), 1843-1847 (1989).

 

 

  1. 11.   M. K. Bhalgat, J. C. Roberts, J. A. Mercer-Smith, B. D. Knotts, R. L. Vessella, D. K. Lavallee, “Preparation and biodistribution of copper-67-labeled porphyrins and porphyrin-A6H immunoconjugates,” Nucl. Med. Biol. 24(2), 179-185 (1997).

 

  1. 12.   I. Novak-Hofer, P. A. Schubiger, “Copper-67 as a therapeutic nuclide for radioimmunotherapy,” Eur. J. Nucl. Med. Mol. Imaging, 29(6), 821-830 (2002).

 

  1. 13.   G. L. DeNardo, S. J. DeNardo, R. T. O'Donnell, L. A. Kroger, D. L. Kukis, C. F. Meares, D. S. Goldstein, S. Shen, “Are radiometal-labeled antibodies better than iodine-131-labeled antibodies: comparative pharmacokinetics and dosimetry of copper-67-, iodine-131-, and yttrium-90-labeled Lym-1 antibody in patients with non-Hodgkin's lymphoma,” Clin. Lymphoma. 1(2), 118-126 (2000).

 

  1. 14.   A. B. Delaloye, B. Delaloye, F. Buchegger, C. A. Vogel, M. Gillet, J. P. Mach, A. Smith, P. A. Schubiger, “Comparison of copper-67- and iodine-125-labeled anti-CEA monoclonal antibody biodistribution in patients with colorectal tumors, ” J. Nucl. Med. 38(6), 847-853 (1997).

 

  1. 15.   G.D. Robinson, F.W. Zielinski, A.W. Lee, “The zinc-62/copper-62 generator: a convenient source of copper-62 for radiopharmaceuticals,” Int. J. Appl. Radiat. Isot. 31(2), 111-116 (1980).

 

  1. 16.   O.P.Anderson, A.B. Packard , “Structural variations in macrocyclic copper (II),” Inorg. Chem. 18, 1940-1947 (1979).

 

  1. 17.   O. Obata, E. Yoshimi, A. Waki, J. S. Lewis, N. Oyama, M. J. Welch, H. Saji, Y. Yonekura, Y. Fujibayashi, “Retention mechanism of hypoxia selective nuclear imaging/radiotherapeutic agent Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) in tumor cells,”  Ann. Nucl. Med. 15, 499-504 (2001).

 

  1. 18.   J. S. Lewis, J. M. Connett, J. R. Garbow, T. L. Buettner, Y. Fujibayashi, J. W. Fleshman, M. J. Welch, “Copper-64-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for the prevention of tumor growth at wound sites following laparoscopic surgery: monitoring therapy response with micro PET and magnetic resonance imaging,” Cancer Res. 62, 445-449 (2002).
  2. 19.   A.B. Packard, J. F. Kronauge, E. Barbarics, S. Kiani, S. T. Treves, “Synthesis and biodistribution of a Lipophilic 64Cu-labeled monocationic Copper(II) complex,” Nucl. Med. Biol. 29, 289-294 (2002).

 

  1. 20.   R.S. Beanlands, O. Muzik, M. Mintun, T. Mangner, K. Lee, N. Petry, G.D. Hutchins, M. Schwaiger, “The kinetics of copper-62-PTSM in the normal human heart,” J. Nucl. Med. 33(5), 684-90 (1992).

 

  1. 21.   T.R. Wallhaus, J. Lacy, R. Stewart, J. Bianco, M.A. Green, N. Nayak, C.K. Stone, “Copper-62-pyruvaldehyde bis(N-methyl-thiosemicarbazone) PET imaging in the detection of coronary artery disease in humans,” J. Nucl. Cardiol. 8(1), 67-74 (2001).

 

  1. 22.   M. A. Green, M. J. Welch, C. J. Mathias, S. R. Bergmann, J. S. Perlmutter, M. E. Raichle, F. F. Rubio, M. Janik, “Copper-62-PTSM: Production and evaluation of a generator produced multi-purpose PET perfusion agent,” J. Nucl. Med. 31, 815 (1990).

 

  1. 23.   C. J. Mathias, M. J. Welch, D. J. Perry, A. H. McGuire, X. Zhu, J. M. Connett, M. A. Green, “Investigation of copper-PTSM as a PET tracer for tumor blood flow,” Nucl. Med. Biol. 18(7), 807-811 (1991).

 

  1. 24.   M.A. Green, “A potential copper radiopharmaceutical for imaging the heart and brain: copper-labeled pyruvaldehyde Bis (N4-methylthiosemicarbazone),” Nucl. Med. Biol. 14(1), 59-61 (1987).

 

  1. 25.   A. R. Jalilian, B. Fateh, M. Ghergherehchi, A. Karimian, M. Matloobi, S. Moradkhani,  M. Kamalidehghan, “Preparation, distribution, stability and tumor imaging properties of [62Zn]Bleomycin in normal and tumor-bearing mice,” Iran. J. Radiat. Res. 1(1), 37-44 (2003).

 

  1. 26.   B. A. Gingras, T. Suprunchuk, C. H. Bayley, “The preparation of some thiosemicarbazones and their copper complexes,” Part III. Can. J. Chem. 40, 1053-1057 (1962).

 

  1. 27.   B. Pastakia, L.M. Lieberman, S.J. Gatley, D. Young, D.H. Petering, D. Minkel “Tissue distribution of copper-labeled 3-ethoxy-2-oxobutyraldehyde bis (thiosemicarbazone) (Cu-64 KTS) in mice and rats: concise communication,” J. Nucl. Med. 21(1), 67-70 (1980).